Immunodeficiency Disorders Overview

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Questions and Answers

What is the primary consequence of platelet dysfunction?

Inflammatory response disorders

Bleeding disorders (correct)

Increased likelihood of autoimmune diseases

Enhanced bacterial infections

What characterizes Chédiak-Higashi syndrome?

Impaired complement function

Excessive platelet aggregation

Defective neutrophil chemotaxis (correct)

B-cell maturation abnormalities

Which complement deficiencies are associated with increased infections from encapsulated organisms?

Deficiency of C1, 4, or 2 (correct)

Deficiency of C5

Deficiency of C3

Deficiency of C7

How are most complement deficiencies inherited?

Autosomal dominant traits Signup and view all the answers

What role does the membrane attack complex (MAC) play in the immune response?

Destroys Gram-negative bacteria Signup and view all the answers

Which condition is characterized by impaired development and/or function of T lymphocytes?

Combined immunodeficiencies Signup and view all the answers

What is often the cause of defective antibody responses in conditions like X-linked agammaglobulinemia?

Intrinsic B cell abnormalities Signup and view all the answers

Patients with defects in B cell function are likely to experience which of the following?

Recurrent pyogenic infections Signup and view all the answers

What role do IgG and IgM play in the absence of IgA?

They compensate for the lack of IgA, often making the deficiency go unnoticed. Signup and view all the answers

What is a consequence of defects in T cell function?

Susceptibility to opportunistic infections. Signup and view all the answers

What condition is characterized by the absence of the thymus?

Di George Syndrome Signup and view all the answers

Which of the following best describes SCID?

It presents with severe bacterial, viral, and fungal infections within the first six months of life. Signup and view all the answers

What is one major cause of secondary immunodeficiency?

Malnutrition. Signup and view all the answers

Which factor can lead to immunodeficiency due to prolonged serious disorder?

Chronic disease such as diabetes. Signup and view all the answers

What is a defining feature of T cell immunodeficiencies?

Defective T-dependent B cell responses. Signup and view all the answers

What is the most profound effect of SCID on the immune response?

Lack of T cells. Signup and view all the answers

What is the primary consequence of severe protein-energy malnutrition (PEM) on the immune system?

Reduced efficacy of the immune system Signup and view all the answers

Which trace elements are crucial for maintaining a strong immune response?

Iron, selenium, copper, and zinc Signup and view all the answers

How does the human immunodeficiency virus (HIV) primarily affect the immune system?

By targeting CD4 T cells and macrophages Signup and view all the answers

What role do vitamins A, B6, C, E and folic acid play in the immune system?

They enhance overall resistance to infection Signup and view all the answers

What is a common effect of immunomodulatory drugs on immune function?

They severely depress immune functions Signup and view all the answers

Which of the following correctly describes the transmission routes of HIV?

Sexual contact, contaminated needles/blood products, and vertical transmission Signup and view all the answers

What is a significant risk that develops if HIV remains untreated?

Acquired immunodeficiency syndrome (AIDS) Signup and view all the answers

What is the primary consequence of X-linked (Bruton) Agammaglobulinemia?

Inability to produce B cells and plasma cells Signup and view all the answers

What effect do carotenoids have on immune function?

They enhance NK cell activity and stimulate cytokine production Signup and view all the answers

What critical protein is lacking in X-linked (Bruton) Agammaglobulinemia, preventing B cell maturation?

Cytoplasmic tyrosine kinase Signup and view all the answers

Which clinical presentation is most commonly associated with X-linked hyper-IgM syndrome?

Defective heavy-chain isotype switching Signup and view all the answers

What key function is impaired in patients with X-linked hyper-IgM syndrome due to defects in CD40 ligand?

B cell activation and isotype switching Signup and view all the answers

Which of the following describes the immune response in patients with selective IgA deficiency?

Chronic infections at mucosal surfaces Signup and view all the answers

Why do symptoms of X-linked (Bruton) Agammaglobulinemia typically manifest after the first year of life?

Initial antibody production from maternal IgG Signup and view all the answers

Which factor is crucial for the interaction between activated T cells and macrophages in X-linked hyper-IgM syndrome?

CD40 ligand Signup and view all the answers

What kind of infections are prevalent in patients with X-linked hyper-IgM syndrome due to impaired cell-mediated immunity?

Intracellular microbial infections Signup and view all the answers

What is the underlying cause of chronic granulomatous disease?

Mutations in genes encoding NADPH oxidase Signup and view all the answers

Which type of infections are patients with chronic granulomatous disease particularly prone to?

Opportunistic infections with certain bacteria and fungi Signup and view all the answers

What is a characteristic feature of Chediak-Higashi syndrome?

Presence of large granular inclusions in white blood cells Signup and view all the answers

In chronic granulomatous disease, which mechanism is impaired leading to difficulty in killing microbes?

Production of microbicidal reactive oxygen species Signup and view all the answers

What mechanism do catalase-positive bacteria use to evade killing by leukocytes in chronic granulomatous disease?

Degradation of hydrogen peroxide Signup and view all the answers

Which syndrome is characterized by impaired intracellular killing and lymphoreticular cancer due to defective lysosomal function?

Chediak-Higashi syndrome Signup and view all the answers

What is one of the main clinical presentations of myeloperoxidase deficiency?

Recurrent candidial infections Signup and view all the answers

What is a key characteristic of Lazy Leucocyte syndrome?

Poor functional response of leukocytes Signup and view all the answers

What characterizes primary immunodeficiency diseases (PIDs)?

They result from intrinsic defects in the immune system. Signup and view all the answers

Which of the following is a feature of congenital agranulocytosis (Kostmann syndrome)?

Defect in the gene inducing G-CSF. Signup and view all the answers

Which of the following best describes secondary (acquired) immune deficiency?

It results from infections such as HIV. Signup and view all the answers

What is a common consequence of defects in innate immunity?

Impaired function of phagocytes. Signup and view all the answers

What type of deficiencies are caused by genetically-determined defects in the complement system?

Complement deficiencies. Signup and view all the answers

Which of the following illnesses is NOT typically associated with congenital agranulocytosis?

Non-Hodgkin lymphoma. Signup and view all the answers

What treatment is commonly used for patients with congenital agranulocytosis?

Granulocyte-macrophage colony stimulating factor. Signup and view all the answers

Phagocytic dysfunctions are primarily related to deficiencies in what area?

Enzymatic pathways in phagocytes. Signup and view all the answers

Study Notes

Immunodeficiency States

Immunodeficiency disorders are a diverse group of illnesses arising from abnormalities in the immune system, making individuals susceptible to infections.
Immune system abnormalities can involve the absence or malfunction of blood cells (lymphocytes, granulocytes, monocytes) or soluble molecules (antibodies, complement components).
Immune deficiency states are categorized into primary and secondary types.

Primary Immunodeficiency

Primary immunodeficiencies (PIDs) are disorders resulting from hereditary or intrinsic defects in the immune system.
PIDs encompass a diverse group of disorders characterized by defects in the development or function of the immune system.
These defects originate from intrinsic cellular and mediator deficiencies in either innate or adaptive immunity.
The classification of PIDs is based on the underlying immunological defect.

Innate Immunity Defects

Defects in phagocytes and the complement system often result in immunodeficiency.
Phagocytic cell disorders involve inadequacies in the development and/or function of myeloid cells (granulocytes and macrophages).
Genetically-determined defects of the complement system's functional or regulatory components lead to complement deficiencies.
Leukocyte defects include both quantitative and qualitative abnormalities.

Quantitative Leukocyte Defects

Congenital agranulocytosis (Kostmann syndrome) is characterized by a gene defect that hinders G-CSF (granulocyte colony stimulating factor) production, leading to a decline in neutrophil counts and impaired myeloid progenitor cell differentiation.
Affected patients exhibit features such as pneumonia, otitis media, gingivostomatitis, and perineal abscesses.

Phagocytic Dysfunction

Primary or intrinsic issues in phagocytes are linked to enzymatic deficiencies within the metabolic pathways essential for microbial killing.
Chronic granulomatous disease results from NADPH oxidase deficiencies, causing impaired microbial killing within macrophages and neutrophils.
Myeloperoxidase deficiency, Chediak-Higashi syndrome, and Lazy Leukocyte syndrome also fall under the category of phagocytic dysfunction.

Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) is an X-linked disorder typically manifesting in the first two years of life.
CGD arises from mutations affecting gene encoding subunits of NADPH oxidase, which catalyzes the production of reactive oxygen species vital for microbial destruction.
Patients with CGD exhibit susceptibility to infections stemming from impaired intracellular killing of bacteria and fungi. They commonly experience recurrent infections with catalase-positive bacteria, such as staphylococci.

Specific Enzyme Deficiencies

Complete deficiency of glucose-6-phosphate dehydrogenase (G6PD) in leukocytes results in a syndrome mimicking chronic granulomatous disease, exhibiting a later onset.
This condition affects both genders and frequently co-occurs with hemolytic anemia. Meanwhile, myeloperoxidase deficiency results in impaired intracellular killing, leading to candidial and staphylococcal infections.

Chediak-Higashi Syndrome

Chediak-Higashi syndrome is an autosomal recessive multi-system disorder characterized by recurrent bacterial infections, hepatosplenomegaly, central nervous system abnormalities, and a high incidence of lymphoreticular cancers.
The primary defect is abnormal intracellular killing due to defective phagosome-lysosome fusion, indicated by abnormal giant granules in white blood cells.
Patients with this disorder often exhibit albinism, as melanocyte dysfunction prevents pigment transfer to keratinocytes and other epithelial cells.
The syndrome is also associated with platelet abnormalities that can contribute to bleeding disorders due to platelet dysfunction.

Lazy Leukocyte Syndrome

Lazy Leukocyte Syndrome affects neutrophil chemotaxis and is linked with neutropenia.
This condition predisposes individuals to severe bacterial infections.

Complement Deficiency States

Various complement deficiencies and functional abnormalities lead to increased susceptibility to infections.
Complement proteins are essential for opsonization, bacterial killing, and chemotaxis.
Deficiency in early complement components (e.g., C1, C4, C2, or C3) can increase susceptibility to encapsulated organisms (such as Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae).
Deficiencies in late complement components (e.g., C5-C9) impair the formation of the membrane attack complex (MAC).

Defects in Lymphocyte Maturation

Antibody deficiencies reflect impaired B cell function due to abnormalities in intrinsic B cells or defects in T cells that affect B cell activation and maturation.
Combined immunodeficiencies are characterized by impaired development and/or function of T lymphocytes and abnormal B cell function.

Defects in B Cell Function

Defective antibody responses can result from issues like X-linked agammaglobulinemia (lack of B cell maturation) or hyper-IgM syndrome (impaired class switching).
Such deficiencies lead to recurrent pyogenic infections, particularly affecting upper and lower respiratory tract and ear (otitis media).
A variety of diseases linked to B-cell function exist, spanning from complete absence of B cells to selective deficits in specific immunoglobulin classes.

X-linked (Bruton) Agammaglobulinemia

X-linked agammaglobulinemia is a disorder localized to the long arm of the X chromosome.
The condition primarily impacts young boys, leading to a virtual absence of circulating B cells, resulting in severely low levels of all immunoglobulin subclasses (IgG, IgM, IgA, IgD, IgE).
Affected individuals display a lack of antibody production, pre-B cells in the bone marrow, and defective immunoglobulin production caused by a lack of a tyrosine kinase.

Secondary (Acquired) Immunodeficiencies

Major causes of secondary immunodeficiencies include malnutrition, viral infections (e.g., HIV), cancer metastases/leukemias (affecting bone marrow), cancer therapies (chemotherapy/irradiation), corticosteroids (immunosuppressants), and chronic diseases (e.g., diabetes).

Malnutrition

Malnutrition, globally, is a significant cause of immunodeficiency.
Deficiencies in calories, essential macronutrients, or micronutrients severely impair immune responses.
Severely undernourished individuals have an increased risk of infection.

Immunodeficiency Secondary to Drug Therapies

Immunomodulatory drugs can severely suppress immune functions.
Drugs like cyclophosphamide, azathioprine, and mycophenolate mofetil directly affect DNA or its synthesis.
Steroids induce lymphocytopenia, monocytopenia, and neutrophilia and hinder cytokine synthesis and T-cell activation and proliferation.

Human Immunodeficiency Virus (HIV)

HIV infection is a major cause of immunodeficiency worldwide, second only to malnutrition.
HIV primarily affects CD4+ T cells and macrophages.

HIV Infection Pathologic Effects

HIV pathologic effects are directly linked to interaction with CD4 receptors on T cells and cells expressing the CD4 receptor (macrophages, monocytes, microglial cells).
Some HIV strains, termed macrophage-tropic, require CCR5 receptors on cell surfaces to cause infection. Other strains require CXCR4 for binding and cellular uptake.

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Description

This quiz covers immunodeficiency states, focusing on the diverse group of disorders that result from abnormal immune system function. It delves into the classification of primary immunodeficiencies and examines defects in innate immunity, including phagocytes and the complement system. Test your knowledge on these critical aspects of immunology.